ppharmПедиатрическая фармакологияPediatric pharmacology1727-57762500-3089Издательство «ПедиатрЪ»10.15690/pf.v15i2.1873ppharm-1619Research ArticleКЛИНИЧЕСКИЙ СЛУЧАЙCASE REPORTЦитомегаловирусная инфекция у детей первых месяцев жизни: варианты течения, современные подходы к терапии (клинические случаи)Cytomegalovirus Infection in Infants: Course Variants, Modern Approaches to Therapy (Clinical Cases)https://orcid.org/0000-0002-8717-2539БеляеваИ. А.BelyaevaIrina A.

доктор медицинских наук, профессор РАН, профессор кафедры факультетской педиатрии педиатрического факультета РНИМУ им. Н.И. Пирогова, главный научный сотрудник лаборатории неонатологии и проблем здоровья детей раннего возраста, заведующая отделением патологии новорожденных детей ФГАУ «Национальный медицинский исследовательский центр здоровья детей» Минздрава России

belyaeva@nczd.ruhttps://orcid.org/0000-0002-6677-2914БомбардироваЕ. П.BombardirovaElena P.https://orcid.org/0000-0002-4131-5047ПотехинаТ. В.PotekhinaTatiana V.https://orcid.org/0000-0001-8663-2698ГурскаяА. С.GurskayaAleksandra S.Национальный медицинский исследовательский центр здоровья детей, Москва; Российский национальный исследовательский медицинский университет им. Н.И. Пирогова, МоскваРоссияNational Medical Research Center for Children’s Health, Moscow; Pirogov Russian National Research Medical University, MoscowRussian FederationНациональный медицинский исследовательский центр здоровья детей, МоскваРоссияNational Medical Research Center for Children’s Health, MoscowRussian Federation201816052018152168174Copyright © Беляева И.А., Бомбардирова Е.П., Потехина Т.В., Гурская А.С., 20182018Беляева И.А., Бомбардирова Е.П., Потехина Т.В., Гурская А.С.Belyaeva I.A., Bombardirova E.P., Potekhina T.V., Gurskaya A.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pedpharma.ru/jour/article/view/1619

Цитомегаловирусная инфекция (ЦМВИ) у новорожденных и детей первых месяцев жизни может протекать в различных клинических формах, требующих дифференцированной терапии. Представлены особенности двух различных вариантов течения ЦМВИ — генерализованной с манифестной клинической картиной и характерными сдвигами в лабораторных анализах у ребенка в возрасте 2,5 мес с сочетанной генетической патологией и латентной внутри- утробной у ребенка в возрасте 5 дней, приведшей к развитию нейросенсорной тугоухости. Освещены трудности диагностики стертой (латентной) формы болезни и выбора тактики лечения пациента. Представлен успешный результат этиопатогенетической терапии препаратом ганцикловира у ребенка с постнатальной генерализованной ЦМВИ. Подтверждены терапевтическая эффективность и безопасность off-label препаратов ганцикловира и противоцитомегаловирусного иммуноглобулина. Обсуждается целесообразность включения ганцикловира в протокол ведения детей с латентными формами ЦМВИ.

ИСТОЧНИК ФИНАНСИРОВАНИЯ Не указан.

КОНФЛИКТ ИНТЕРЕСОВ Авторы заявили об отсутствии конфликта интересов, который необходимо обнародовать.

Cytomegalovirus infection (CMVI) in newborns and infants can occur in various clinical forms requiring a differentiated therapy. We present the peculiarities of two different variants of CMVI course generalized with a manifest clinical picture and characteristic shifts in laboratory analyzes in a child aged 2.5 months with a combined genetic pathology, and latent intrauterine in a child aged 5 days leading to the development of neurosensory hearing loss. The difficulties in diagnosing a suppressed (latent) form of the disease and choosing a therapeutic approach have been highlighted. A successful result of etiopathogenetic therapy with ganciclovir in a child with postnatal generalized CMVI has been presented. The therapeutic efficacy and safety of off-label ganciclovir preparations and anti-cytomegalovirus immunoglobulin have been confirmed. The advisability of including ganciclovir in the management protocol of children with latent forms of CMVI is discussed.

новорожденныедети первого года жизницитомегаловирусгенерализованная инфекциялатентная внутриутробная инфекцияганцикловирпротивоцитомегаловирусный иммуноглобулинклинические случаиnewbornsinfantscytomegalovirusgeneralized infectionlatent intrauterine infectiongancicloviranti-cytomegalovirus immunoglobulinclinical casesReferencesManicklal S, Emery VC, Lazzarotto T, et al. The «silent» global burden of congenital cytomegalovirus. Clin Microbiol Rev. 2013;26(1):86–102. doi: 10.1128/CMR.00062-12.Manicklal S, Emery VC, Lazzarotto T, et al. The «silent» global burden of congenital cytomegalovirus. Clin Microbiol Rev. 2013;26(1):86–102. doi: 10.1128/CMR.00062-12.Marsico C, Kimberlin DW. Congenital Cytomegalovirus infection: advances and challenges in diagnosis, prevention and treatment. Ital J Pediatr. 2017;43(1):38. doi: 10.1186/s13052-017-0358-8.Marsico C, Kimberlin DW. Congenital Cytomegalovirus infection: advances and challenges in diagnosis, prevention and treatment. Ital J Pediatr. 2017;43(1):38. doi: 10.1186/s13052-017-0358-8.Cannon MJ, Schmid DS, Hyde TB. Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection. Rev Med Virol. 2010;20(4):202–213. doi: 10.1002/ rmv.655.Cannon MJ, Schmid DS, Hyde TB. Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection. Rev Med Virol. 2010;20(4):202–213. doi: 10.1002/ rmv.655.Lopes AA, Belhabri S, Karaoui L. Clinical findings and autopsy of a preterm infant with breast milk-acquired cytomegalovirus infection. Am J Perinatol Rep. 2016;6(2):e198–e202. doi: 10.1055/ s-0035-1566249.Lopes AA, Belhabri S, Karaoui L. Clinical findings and autopsy of a preterm infant with breast milk-acquired cytomegalovirus infection. Am J Perinatol Rep. 2016;6(2):e198–e202. doi: 10.1055/ s-0035-1566249.Lim Y, Lyall H. Congenital cytomegalovirus — who, when, what-with and why to treat? J Infect. 2017;74 Suppl 1:S89–S94. doi: 10.1016/S0163-4453(17)30197-4.Lim Y, Lyall H. Congenital cytomegalovirus — who, when, what-with and why to treat? J Infect. 2017;74 Suppl 1:S89–S94. doi: 10.1016/S0163-4453(17)30197-4.James SH, Kimberlin DW. Advances in the prevention and treatment of congenital cytomegalovirus infection. Curr Opin Pediatr. 2016;28(1):81–85. doi: 10.1097/MOP.0000000000000305.James SH, Kimberlin DW. Advances in the prevention and treatment of congenital cytomegalovirus infection. Curr Opin Pediatr. 2016;28(1):81–85. doi: 10.1097/MOP.0000000000000305.Capretti MG, Marsico C, Guidelli Guidi S, et al. Neonatal and long-term ophthalmological findings in infants with symptomatic and asymptomatic congenital cytomegalovirus infection. J Clin Virol. 2017;97:59–63. doi: 10.1016/j.jcv.2017.11.001.Capretti MG, Marsico C, Guidelli Guidi S, et al. Neonatal and long-term ophthalmological findings in infants with symptomatic and asymptomatic congenital cytomegalovirus infection. J Clin Virol. 2017;97:59–63. doi: 10.1016/j.jcv.2017.11.001.Неонатология: национальное руководство. Краткое издание / Под ред. Володина Н.Н. — М.: ГЭОТАР-Медиа; 2014. — 896 с.Neonatologiya: natsional’noe rukovodstvo. Kratkoe izdanie. Ed by Volodin N.N. Moscow: GEOTAR-Media; 2014. 896 p. (In Russ).Клинические рекомендации [проект] по диагностике, лечению и профилактике врожденной цитомегаловирусной инфекции. Доступно по: http://www.raspm.ru/files/CMVI.pdf. Ссылка активна на 02.02.2018.Klinicheskie rekomendatsii [proekt] po diagnostike, lecheniyu i profilaktike vrozhdennoi tsitomegalovirusnoi infektsii. (In Russ).] Доступно по: http://www.raspm.ru/files/CMVI.pdf. Ссылка активна на 02.02.2018.Kimberlin DW, Acosta EP, Sanchez PJ, et al. Pharmacokinetic and pharmacodynamic assessment of oral valganciclovir in the treatment of symptomatic congenital cytomegalovirus disease. J Infect Dis. 2008;197(6):836–845. doi: 10.1086/528376.Kimberlin DW, Acosta EP, Sanchez PJ, et al. Pharmacokinetic and pharmacodynamic assessment of oral valganciclovir in the treatment of symptomatic congenital cytomegalovirus disease. J Infect Dis. 2008;197(6):836–845. doi: 10.1086/528376.Kimberlin DW, Jester PM, Sanchez PJ, et al. Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med. 2015;372(10):933–943. doi: 10.1056/NEJMoa1404599.Kimberlin DW, Jester PM, Sanchez PJ, et al. Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med. 2015;372(10):933–943. doi: 10.1056/NEJMoa1404599.Coll O, Benoist G, Ville Y, et al. Guidelines on CMV congenital infection. J Perinat Med. 2009;37(5):433–445. doi: 10.1515/ JPM.2009.127.Coll O, Benoist G, Ville Y, et al. Guidelines on CMV congenital infection. J Perinat Med. 2009;37(5):433–445. doi: 10.1515/ JPM.2009.127.Buxmann H, Von Stackelberg OM, Schlosser RL, et al. Use of cytomegalovirus hyperimmunoglobulin for prevention of congenital cytomegalovirus disease: a retrospective analysis. J Perinat Med. 2012;40(4):439–446. doi: 10.1515/jpm-2011-0257.Buxmann H, Von Stackelberg OM, Schlosser RL, et al. Use of cytomegalovirus hyperimmunoglobulin for prevention of congenital cytomegalovirus disease: a retrospective analysis. J Perinat Med. 2012;40(4):439–446. doi: 10.1515/jpm-2011-0257.Gantt S, Bitnun A, Renaud C, et al. Diagnosis and management of infants with congenital cytomegalovirus infection. Paediatr Child Health. 2017;22(2):72–74. doi: 10.1093/pch/pxx002.Gantt S, Bitnun A, Renaud C, et al. Diagnosis and management of infants with congenital cytomegalovirus infection. Paediatr Child Health. 2017;22(2):72–74. doi: 10.1093/pch/pxx002.Williams EJ, Kadambari S, Berrington JE, et al. Feasibility and acceptability of targeted screening for congenital CMV-related hearing loss. Arch Dis Child Fetal Neonatal Ed. 2014;99(3):F230– F236. doi: 10.1136/archdischild-2013-305276.Williams EJ, Kadambari S, Berrington JE, et al. Feasibility and acceptability of targeted screening for congenital CMV-related hearing loss. Arch Dis Child Fetal Neonatal Ed. 2014;99(3):F230– F236. doi: 10.1136/archdischild-2013-305276.Kawada JI, Torii Y, Kawano Y, et al. Viral load in children with congenital cytomegalovirus infection identified on newborn hearing screening. J Clin Virol. 2015;65:41–45. doi: 10.1016/j. jcv.2015.01.015.Kawada JI, Torii Y, Kawano Y, et al. Viral load in children with congenital cytomegalovirus infection identified on newborn hearing screening. J Clin Virol. 2015;65:41–45. doi: 10.1016/j. jcv.2015.01.015.Muldoon KM, Armstrong-Heimsoth A, Thomas J. Knowledge of congenital cytomegalovir us (cCMV) among physical and occupational therapists in the United States. PLoS One. 2017;12(10):e0185635. doi: 10.1371/journal.pone.0185635.Muldoon KM, Armstrong-Heimsoth A, Thomas J. Knowledge of congenital cytomegalovir us (cCMV) among physical and occupational therapists in the United States. PLoS One. 2017;12(10):e0185635. doi: 10.1371/journal.pone.0185635.Gantt S, Dionne F, Kozak FK, et al. Cost-effectiveness of Universal and Targeted Newborn Screening for Congenital Cytomegalovirus Infection. JAMA Pediatr. 2016;170(12):1173–1180. doi: 10.1001/ jamapediatrics.2016.2016.Gantt S, Dionne F, Kozak FK, et al. Cost-effectiveness of Universal and Targeted Newborn Screening for Congenital Cytomegalovirus Infection. JAMA Pediatr. 2016;170(12):1173–1180. doi: 10.1001/ jamapediatrics.2016.2016.Forner G, Abate D, Mengoli C, et al. High cytomegalovirus (CMV) DNAemia predicts CMV sequelae in asymptomatic congenitally infected newborns born to women with primary infection during pregnancy. J Infect Dis. 2015;212(1):67–71. doi: 10.1093/infdis/ jiu627.Forner G, Abate D, Mengoli C, et al. High cytomegalovirus (CMV) DNAemia predicts CMV sequelae in asymptomatic congenitally infected newborns born to women with primary infection during pregnancy. J Infect Dis. 2015;212(1):67–71. doi: 10.1093/infdis/ jiu627.Yilmaz Ciftdogan D, Vardar F. Effect on hearing of oral valganciclovir for asymptomatic congenital cytomegalovirus infection. J Trop Pediatr. 2011;57(2):132–134. doi: 10.1093/ tropej/fmq050.Yilmaz Ciftdogan D, Vardar F. Effect on hearing of oral valganciclovir for asymptomatic congenital cytomegalovirus infection. J Trop Pediatr. 2011;57(2):132–134. doi: 10.1093/ tropej/fmq050.Lackner A, Acham A, Alborno T, et al. Effect on hearing of ganciclovir therapy for asymptomatic congenital cytomegalovirus infection: four to 10 year follow up. J Laryngol Otol. 2009;123(4):391– 396. doi: 10.1017/S0022215108003162.Lackner A, Acham A, Alborno T, et al. Effect on hearing of ganciclovir therapy for asymptomatic congenital cytomegalovirus infection: four to 10 year follow up. J Laryngol Otol. 2009;123(4):391– 396. doi: 10.1017/S0022215108003162.Awad Z, Huins C, Pothier DD. Antivirals for idiopathic sudden sensorineural hearing loss. Cochrane Database Syst Rev. 2012;(8):CD006987. doi: 10.1002/14651858.CD006987.pub2.Awad Z, Huins C, Pothier DD. Antivirals for idiopathic sudden sensorineural hearing loss. Cochrane Database Syst Rev. 2012;(8):CD006987. doi: 10.1002/14651858.CD006987.pub2.Blazquez-Gamero D, Galindo Izquierdo A, Del Rosal T, et al. Prevention and treatment of fetal cytomegalovirus infection with cytomegalovirus hyperimmune globulin: a multicenter study in Madrid. J Matern Fetal Neonatal Med. 2017:1–9. doi: 10.1080/14767058.2017.1387890.Blazquez-Gamero D, Galindo Izquierdo A, Del Rosal T, et al. Prevention and treatment of fetal cytomegalovirus infection with cytomegalovirus hyperimmune globulin: a multicenter study in Madrid. J Matern Fetal Neonatal Med. 2017:1–9. doi: 10.1080/14767058.2017.1387890.

The authors declare that there are no conflicts of interest present.